Tumors vary between individuals and all treatments will not work for all patients. Personalized medicine involves designing a treatment based of the analysis of a sample from the patient (e.g. biopsy, blood). It has shown promise in treating individual tumors but it has not been as successful as hoped. This approach improves patient outcome but can be complicated by both phenotypic and genetic heterogeneity within the tumor itself. A population of a tumor can be susceptible to treatment while a small subpopulation will be resistant. This results in a treatment that will destroy the bulk of a tumor but leave the resistant subpopulation which can cause recurrence of cancer.
A next step that needs to be taken in personalized cancer therapy is to characterize all populations of the tumor and design a specific treatment to enhance survival rates and reduce recurrence. This can only be accomplished through new and enhanced tumor analysis techniques. Combining cytomics and rare-cell genetic analysis, my research works to build the pathway from patient-specific treatment to tumor-specific therapy. Multiple myeloma displays high genetic diversity as well as clonal heterogeneity and frequently develops drug resistance making it an excellent target for this approach.
I am currently working with a multiple myeloma coculture (MCCC) device originally developed by Dr. Young in David Beebe’s lab. This device enables a researcher to perform functional analyses on small numbers of non-adherent cells, specifically multiple myeloma cells, in a controlled microenvironment. The MCCC enabled coculture with bone marrow stromal cells which have been implicated in development of drug resistance in multiple myeloma through either paracrine mediated signaling. The device was able to determine the NF-κB activation in response to the drug, Bortezomib in the presence and absence of bone marrow stromal cells.
A culture system which is capable of producing readouts on a gene, mRNA, and protein level and highlights rare-cell contributions to the tumor would be a very useful tool in research and in clinic. I have the background, experience, and environment to create this device, a traineeship in GSTP will give me the tools to better design experiments and analyze the data.